期刊
MUCOSAL IMMUNOLOGY
卷 14, 期 3, 页码 751-761出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-021-00387-6
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资金
- Children's Discovery Institute of Washington University
- St. Louis Children's Hospital Postdoctoral Research grant [MI-F-2018-712]
- NIH [R01 AI127552, R01 AI139314, R00 AI141683, R01 DK122790]
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [NRF-2016R1A6A3A03012352]
- G. Harold and Leila Y. Mathers Foundation
- Pew Biomedical Scholars Program of The Pew Charitable Trusts
Astroviruses, which cause viral gastroenteritis in children globally, have been understudied due to the lack of well-defined animal models. This study establishes a platform to cultivate muAstV using mouse enteroid-derived air-liquid interface (ALI) cultures, providing insights into chronic infection characteristics and the correlation with interferon-lambda expression in the small intestine.
Although they globally cause viral gastroenteritis in children, astroviruses are understudied due to the lack of well-defined animal models. While murine astroviruses (muAstVs) chronically infect immunodeficient mice, a culture system and understanding of their pathogenesis is lacking. Here, we describe a platform to cultivate muAstV using air-liquid interface (ALI) cultures derived from mouse enteroids, which support apical infection and release. Chronic muAstV infection occurs predominantly in the small intestine and correlates with higher interferon-lambda (IFN-lambda) expression. MuAstV stimulates IFN-lambda production in ALI, recapitulating our in vivo findings. We demonstrate that goblet cells and enterocytes are targets for chronic muAstV infection in vivo, and that infection is enhanced by parasite co-infection or type 2 cytokine signaling. Depletion of goblet cells from ALI limits muAstV infection in vitro. During chronic infection, muAstV stimulates IFN-lambda production in infected cells and induces ISGs throughout the intestinal epithelium in an IFN-lambda-receptor-dependent manner. Collectively, our study provides insights into the cellular tropism and innate immune responses to muAstV and establishes an enteroid-based culture system to propagate muAstV in vitro.
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